The three projects in the Program will utilize a combination of transgenic and gene-targeted approaches to study the role of candidate genes with the potential important functional roles in cardiac function, which are identified in these projects. Core Unit B will provide services to assist in the design of the appropriate constructs and the subsequent generation of gene-targeted and transgenic mice. The objectives are five-fold: 1) to design and test appropriate transgenes in in vitro systems; 2) to generate appropriate lines of transgenic and gene-targeted mice for various projects in the Program; 3) to identify founders and to breed/maintain appropriate lines of mice; 4) to knockout specific candidate regulatory genes via homologous recombination; and 5) to breed and generate lines of mice required for regionally restricted and/or tissuespecific conditional gene targeting and over-expression via CRE-lox strategies.